Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients
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|ClinicalTrials.gov Identifier: NCT01610141|
Recruitment Status : Unknown
Verified October 2013 by Tong Yin, Chinese PLA General Hospital.
Recruitment status was: Recruiting
First Posted : June 1, 2012
Last Update Posted : October 9, 2013
|Condition or disease||Intervention/treatment||Phase|
|Atrial Fibrillation Deep Vein Thrombosis Pulmonary Embolism Heart Valve Disease||Other: Genotype-guided warfarin dosing Other: Non-genotype guided warfarin dosing||Phase 4|
Warfarin is the most widely used oral anticoagulation drug for preventing and treating thromboembolic events, but there is greater than 10-fold interindividual variability in the dose required to attain a therapeutic response. In 2007, the US Food and Drug Administration updated the label of warfarin, recommending consideration of pharmacogenetic information which has been confirmed to contribute significantly to the variability in warfarin dose requirements. Thereafter, multiple pharmacogenetic dosing algorithms were constructed to predict warfarin dose by integrating clinical and genetic factors. Taken together, approximately between one-third and one- half of the variability in warfarin dose could be explained by the proposed algorithms. However, the potential benefit of these dosing algorithms in terms of their safety and clinical utility has not been adequately investigated in randomised settings in Chinese patients.
- To apply routine pharmacogenetic (PG)-guided dosing of warfarin in clinical practice in Chinese patients.
- To compare the percentage out-of-range (%OOR) International Normalized Ratios (INRs) during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.
- To compare the cost effectiveness, number of thromboembolic and bleeding events, time within therapeutic INR range, time to reach stable dose and number of supratherapeutic INR peaks during the first 3 month of warfarin therapy using PG-guided dosing with historical standard (STD), empiric dosed controls.
This is a prospective, randomized study of Chinese patients who are to initiate chronic warfarin anticoagulation for specific, qualifying clinical reasons (i.e., atrial fibrillation, Deep vein thrombosis/pulmonary embolism, or Prosthetic valve replacement). Qualifying patients will be consented and randomized to an individualized, pharmacogenetic guided warfarin-dosing regimen (PG group) or to standard care (without knowledge of genotype)(STD group). All patients will receive a baseline INR. For patients in PG group, a maintenance dose for each patient will be predicted by the pharmacogenetic algorithm derived previously in Chinese. A maintenance dose of 3 mg/day will designed to each patients in STD group. The starting dose of warfarin that is twice the assigned daily maintenance dose will be prescribed on the first and second days, and then the dose will revert to the assigned maintenance dose.
Each patient will participate for at least 3 months.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||500 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Applying Pharmacogenetics to Warfarin Dosing in Chinese Patients|
|Study Start Date :||June 2012|
|Estimated Primary Completion Date :||June 2014|
|Estimated Study Completion Date :||June 2015|
Experimental: Genotype-guided warfarin dosing
A pharmacogenetic dosing algorithm including clinical factors and genotype information (VKORC1, CYP2C9 and CYP4F2) will be used to determine warfarin doses.
Other: Genotype-guided warfarin dosing
Applying a Pharmacogenetic-guided warfarin dosing algorithm derived from Chinese to determine the daily maintenance dose of warfarin, based on clinical factors (age, sex, body surface area, etc.), and VKORC1, CYP2C9 and CYP4F2 genotypes, to individualize the dosing of warfarin.
Active Comparator: Non-genotype guided warfarin dosing
A fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement.
Other: Non-genotype guided warfarin dosing
A Empiric fixed warfarin dose of 3 mg/day was given to the patients for at least 3 days. Following doses were adjusted according to the INR measurement.
- A comparison between the pharmacogenetic and standard arms of the per-patient percentage of out-of-range INRs (<1.5, >3). [ Time Frame: 3 months ]
- Time to the first supratherapeutic INR [ Time Frame: 3 months ]
- The proportion of time within the therapeutic INR range [ Time Frame: 3 months ]
- The proportion of patients reaching therapeutic INR on days 5 and 8 [ Time Frame: 3 months ]
- The total number of INR measurements and number of dose adjustments made [ Time Frame: 3 months ]
- Proportion of INRs > 4 [ Time Frame: 3 months ]
- Major bleeding events [ Time Frame: 3 months ]
- Minor bleeding events [ Time Frame: 3 months ]
- Thromboembolic complications [ Time Frame: 3 months ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01610141
|Contact: Tong Yin, Dr.||firstname.lastname@example.org|
|Contact: Xiaoqi Li, Dr.||email@example.com|
|Institute of geriatric Cardiology, General Hospital of People's Liberation Army||Recruiting|
|Beijing, China, 100853|
|Contact: Tong Yin, Dr. 86-13693693085 firstname.lastname@example.org|
|Contact: Xiaoqi Li, Dr. 86-15901075996 email@example.com|
|Principal Investigator: Tong Yin, Dr.|
|Principal Investigator:||Tong Yin, Dr.||Institute of Geriatric Cardiology, General Hospital of People's Liberation Army, Beijing China|